Back Side Effects - HIV GI, Metabolic & Lipodystrophy

GI, Metabolic & Lipodystrophy

FDA Approves Diarrhea Drug Crofelemer for People with HIV/AIDS

On December 31, the U.S. Food and Drug Administration (FDA) approved crofelemer (brand name Fulyzaq) for treatment of diarrhea in people with HIV/AIDS on antiretroviral therapy (ART) -- the first approved medication for this indication.

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HIV11: Lipid Levels Are Higher among HIV+ People on ART, Immune Suppression May Play a Role

People with HIV on suppressive antiretroviral therapy (ART) have "considerably higher" blood lipid levels relative to untreated individuals or those on less effective treatment, researchers reported at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) last month in Glasgow. They also found that greater immune deficiency, as indicated by lowest-ever CD4 count, was associated with lipid elevations.

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Tesamorelin (Egrifta) Now Available to Manage HIV-related Lipodystrophy

Tesamorelin, the recently approved treatment for lipodystrophy, is now commercially available under the brand name Egrifta, according to a recent announcement from EMD Serono. The company will offer a patient assistance program for low-income individuals and a co-pay assistance program for people with insurance, as well as patient training on how to inject the new medication.

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Visceral Fat Reduction in HIV+ People on Tesamorelin Improves Metabolic Profile

The synthetic growth hormone-releasing factor tesamorelin (Egrifta) reduces internal abdominal fat in people with HIV, which in turn leads to improvements in lipid and glucose levels, researchers reported in the June 2012 issue of Clinical Infectious Diseases.alt

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FDA Approves Tesamorelin (Egrifta) for Management of Lipodystrophy in People with HIV

The U.S. Food and Drug Administration (FDA) this week approved the growth hormone releasing factor tesamorelin (brand name Egrifta, formerly TH9507) for treatment of lipodystrophy, or excess body fat accumulation, in HIV positive people taking antiretroviral therapy (ART). Developed by Theratechnologies, the drug will be marketed in the U.S. by EMD Serono. Clinical trials showed that tesamorelin significantly reduced abdominal fat with fewer side effects than human growth hormone itself, though fat returned when the drug was discontinued.

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HIV Infection Linked to Increased Stroke Risk

HIV positive people may have a higher risk of stroke independent of traditional risk factors, with the largest relative increase among younger people and women, according to study findings published in the May 10, 2012, advance online edition of the Journal of Acquired Immune Deficiency Syndromes.alt

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FDA Committee Unanimously Votes to Approve Tesamorelin (Egrifta) for Lipodystrophy

The U.S. Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee recommended by a 16-0 vote last Thursday that the agency should approve tesamorelin (brand name Egifta), a synthetic human growth hormone-releasing factor developed by Theratechnologies, for the treatment of visceral abdominal fat accumulation in people with HIV-related lipodystrophy. The recommendation is based on Phase 3 study results showing that people taking tesamorelin were nearly twice as likely to experience at least an 8% reduction in visceral fat. The main side effect of concern is elevated blood glucose and diabetes.

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CROI 2012: Crofelemer Reduces Diarrhea in People with HIV; FDA Grants Priority Review

A plant compound known as crofelemer significantly decreased the frequency of secretory diarrhea in HIV positive patients, researchers reported at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) last month in Seattle. The U.S. Food and Drug Administration (FDA) has given crofelemer priority review status and is expected to take action by early June.alt

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Growth Hormone Releasing Factor Tesamorelin Reduces Visceral Fat in HIV Positive People with Lipodystrophy

The growth hormone releasing factor tesamorelin (brand name Egrifta, formerly TH9507)reduced the amount of visceral abdominal fat in HIV positive people with central fat accumulation and led to improved feelings about body image, researchers reported in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes. Tesamorelin lowered total cholesterol and did not cause significant side effects, including blood glucose abnormalities.

Abdominal fat accumulation -- an aspect of lipodystrophy syndrome -- is a concern for many HIV positive people, both in terms of body image and cardiovascular risk. Administration of human growth hormone has been shown to reduce visceral adipose tissue (fat deep within the abdomen), but it can lead to side effects including elevated blood glucose, swelling, bone pain, and carpal tunnel syndrome.

In contrast to administering growth hormone directly, tesamorelin is a growth hormone releasing factor that stimulates the pituitary gland in the brain to secrete more growth hormone. Investigators hypothesized that it might provide similar benefits with fewer adverse effects, and this was supported by initial studies.

Julian Falutz from McGill University School of Medicine and colleagues investigated the effects of tesamorelin in 404 HIV positive participants on antiretroviral therapy (ART) who had excess abdominal fat.

This double-blind Phase 3 trial consisted of 2 sequential parts. During the first 6 months, patients were randomly assigned (2:1) to receive daily subcutaneous injections of 2 mg tesamorelin or placebo. In the extension phase (months 6-12), participants initially receiving tesamorelin were randomly assigned (1:1) to either continue on the same tesamorelin regimen or switch to placebo, while patients initially randomized to placebo switched to tesamorelin.

The primary endpoint was changes in visceral adipose tissue, assessed with both CT and DEXA scans. Secondary endpoints included other body composition measurements, body image, levels of insulin-like growth factor-1 (a protein produced in response to growth hormone stimulation), and safety parameters.

Results

  • Visceral adipose tissue decreased by 10.9% (21 cm2 or about 1 kg) on average in the tesamorelin group versus a 0.6% (1 cm2 or about 0.2 kg) decrease in the placebo group during the first 6 months (P < 0.0001).
  • Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-to-hip ratio (P = 0.001) all improved significantly, with no changes in limb or subcutaneous abdominal fat.
  • Patients reported significantly less distress about belly appearance in the tesamorelin group compared with the placebo group (P = 0.02).
  • Physicians' ratings of patient belly appearance also improved significantly (P = 0.02).
  • Among participants who continued on tesamorelin for 12 months, visceral adipose tissue decreased by 17.5% (P < 0.001).
  • However, the visceral adipose tissue improvements of the first 6 months were rapidly lost in patients who switched from tesamorelin to placebo.
  • Patients receiving tesamorelin did not experience a significant decrease in triglycerides compared with placebo (as was seen in a prior Phase 3 study), but there was a trend in this direction.
  • Participants who received tesamorelin for 12 months experienced a significant decrease in total cholesterol.
  • Tesamorelin was well-tolerated overall.
  • Levels of insulin-like growth factor-1 increased significantly, but there was no apparent change in glucose parameters.
  • About 4% of participants experienced hypersensitivity reactions, which were generally mild; a few discontinued therapy prematurely for this reason.

Based on these findings, the study authors concluded, "Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose."

With these new data, they added, "there are now consistent results from two large Phase 3, randomized, placebo-controlled studies to suggest that [tesamorelin] is a potentially useful clinical strategy to selectively reduce visceral adipose tissue and improve body image among HIV-infected patients with abdominal fat accumulation in the context of antiretroviral therapy."

Montreal-based developer Theratechnologies has requested approval of tesamorelin from the U.S. Food and Drug Administration; and the agency will told a public meeting on May 27, 2010 to discuss the topic.

Affiliations: Department of Medicine, Montreal General Hospital and McGill University School of Medicine, Montreal, Canada; Massachusetts General Hospital and Harvard Medical School, Boston, MA.

4/2/10

Reference

J Falutz, D Potvin, JC Mamputu, and others. Effects of Tesamorelin, a Growth Hormone-Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension. Journal of Acquired Immune Deficiency Syndromes 53(3): 311-322. March 1, 2010.

Elevated Triglycerides and Waist Circumference Predict Cardiovascular Risk for People with HIV

HIV positive people with high triglyceride levels and large girth were more likely to have other risk factors associated with cardiovascular disease and events such heart attacks, suggesting that these 2 simple measures may be used to distinguish high-risk versus low-risk individuals, according to a study in the September 22, 2011, edition of the open access journal PLoS ONE.alt

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Latino HIV Patients Starting Antiretroviral Therapy Are Most Likely, and Blacks Are Least Likely, to Develop Lipodystrophy

Body shape changes and metabolic abnormalities -- collectively known as lipodystrophy syndrome -- is common in people with HIV, but it is not yet fully understood whether this is an effect of HIV infection itself, a side effect of antiretroviral therapy, or due to some combination of factors. It is also unclear whether race/ethnicity influences lipodystrophy among HIV positive patients, though it is recognized that metabolic disorders such as diabetes are more common among certain groups in the general HIV negative population.

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CROI 2011: Reduced Limb Muscle, More Belly Fat Linked to Higher Mortality

HIV positive people who lose muscle in their arms and legs while gaining abdominal fat are at increased risk of death, according to findings from the FRAM study presented at CROI 2011. alt

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Growth Hormone Improves Lipodystrophy, but has Detrimental Effect on Blood Glucose

For reasons that are not fully understood, antiretroviral therapy and HIV infection itself are associated with lipodystrophy, a syndrome characterized by visceral adiposity (fat accumulation) and metabolic complications associated with an elevated risk for cardiovascular disease.

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